Phase Ib study of anti-EGFR antibody (SCT200) in combination with anti-PD-1 antibody (SCT-I10A) for patients with RAS/BRAF wild-type metastatic colorectal cancer

• Published in: Cancer biology & medicine 2023-12, Vol.21 (7), p.1-15
• Main Authors: Bai, Ming, Lu, Yao, Shi, Chunmei, Yang, Jianwei, Li, Wei, Yin, Xianli, Huang, Chenghui, Shen, Lin, Xie, Liangzhi, Ba, Yi
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; epidermal growth factor receptor; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - genetics; ErbB Receptors - immunology; Female; Humans; Immune Checkpoint Inhibitors - therapeutic use; Male; Middle Aged; Original; programmed cell death 1; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Programmed Cell Death 1 Receptor - immunology; Progression-Free Survival; Proto-Oncogene Proteins B-raf - genetics; sct-i10a; sct200
• ISSN: 2095-3941
• DOI: 10.20892/j.issn.2095-3941.2023.0301

This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor (EGFR) antibody (SCT200) and an anti-programmed cell death 1 (PD-1) antibody (SCT-I10A) as third-line or subsequent therapies in patients with rat sarcoma viral oncogene (RAS)/v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type (wt) metastatic colorectal cancer (mCRC). We conducted a multicenter, open-label, phase Ib clinical trial. Patients with histologically confirmed RAS/BRAF wt mCRC with more than two lines of treatment were enrolled and treated with SCT-I10A and SCT200. The primary endpoints were the objective response rate (ORR) and safety. The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Twenty-one patients were enrolled in the study through January 28, 2023. The ORR was 28.57% and the DCR was 85.71% (18/21). The median PFS and OS were 4.14 and 12.84 months, respectively. The treatment-related adverse events (TRAEs) were tolerable. Moreover, compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt mCRC in a third-line setting, no significant improvements in PFS and OS were observed in the combination group. SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt mCRC patients with an acceptable safety profile. Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting. (Registration No. NCT04229537).